Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure: A Randomized Controlled Trial
Allogeneic Bone Marrow-Derived Mesenchymal Stromal Cells for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure: A Randomized Controlled Trial
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DOI：
10.1002/hep.29189
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发表时间：
2017-07-01
期刊：
影响因子：
13.5
通讯作者：
Gao, Zhi-liang
中科院分区：
文献类型：
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作者：
Lin, Bing-liang;Chen, Jun-feng;Gao, Zhi-liang
由于治疗选择有限，B型肝炎病毒（HBV）相关慢性加急性肝衰竭（ACLF）的死亡率很高。临床前和临床研究已经证明，间充质基质细胞（MSCs）治疗有利于肝损伤的恢复。我们假设MSC治疗可以改善HBV相关ACLF的结局。从2010年到2013年，110例HBV相关ACLF患者入组了这项开放标签、非盲随机对照研究。对照组54例，采用常规药物治疗。实验组（n = 56）每周输注1.0至10 × 10（5）细胞/kg同种异体骨髓来源的MSC，持续4周，然后随访24周。MSC组的累积生存率为73.2%（95%置信区间61.6%-84.8%），SMT组为55.6%（95%置信区间42.3%-68.9%）（P = 0.03）。没有输注相关的副作用，但在5-24周的随访期间，MSC患者的发热比SMT患者更频繁。两组中的任何试验患者均未发生癌症。与对照组相比，同种异体骨髓源性MSC治疗显着改善了临床实验室测量值，包括血清总胆红素和终末期肝脏疾病模型评分。MSC组严重感染发生率明显低于SMT组（16.1%vs33.3%，P = 0.04）。SMT组多器官功能衰竭和严重感染的死亡率高于MSC组（37.0%对17.9%，P = 0.02）。结论：外周静脉输注同种异体骨髓间充质干细胞治疗HBV相关ACLF安全、方便，通过改善肝功能、降低严重感染发生率，显著提高24周生存率。
Mortality from hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV-related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV-related ACLF were enrolled in this open-label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 x 10(5) cells/kg allogeneic bone marrow-derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%-84.8%) versus 55.6% (95% confidence interval 42.3%-68.9%) for the SMT group (P = 0.03). There were no infusion-related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5-24 of follow-up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow-derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End-Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). Conclusion: Peripheral infusion of allogeneic bone marrow-derived MSCs is safe and convenient for patients with HBV-related ACLF and significantly increases the 24-week survival rate by improving liver function and decreasing the incidence of severe infections.